Background: Osteoarthritis (OA) is a common, painful, and limiting condition that affects an estimated 20 million Americans. Identification of effective non-pharmacologic strategies is critical for control of OA pain because of the increased intake of medications in older adults with this condition and recent concerns regarding COX inhibitors. Transcutaneous electrical nerve stimulation (TENS) is effective for pain relief in patients with OA and may be particularly effective for the knee. However, more standardized treatment protocols, stimulation parameters, and outcome measures are needed. Studies in animals with arthritis of the knee show that low and high frequency TENS has no effect on spontaneous pain behaviors but reduces hyperalgeisa (increased pain in response to noxious stimuli). Purpose: The primary aim of this study is to compare the effect of high (100Hz) and low (10Hz) frequency TENS to placebo in 120 patients with OA (40 per group) on primary and secondary hyperalgesia, subjective pain scores, and function. We hypothesize that TENS will reduce hyperalgesia and pain with movement, resulting in increased function. Another concern is that there is not an appropriate placebo for TENS. Since TENS delivers an electrical current through the skin to produce pain relief, patients can typically feel the stimulation under the electrodes. Standard placebo-TENS does not deliver a current. A new device has the capability of mimicking a true TENS application. The secondary aim of this study is to compare the effect of short burst placebo-TENS (new device), standard placebo-TENS, and active TENS in 90 healthy volunteers (30 per group) on perception of intervention, and pain thresholds and temporal summation to heat and pressure stimuli. Methods: Two prospective, randomized, double blind, controlled trials will be conducted. Subjects in both trials will receive telephone screening and a single visit for intervention and testing. Trial #1 will assess pain thresholds and temporal summation to pressure and heat stimuli before and after TENS application and perception of treatment after TENS. Trial #2 will assess VAS pain scores, pain thresholds and temporal summation to force, pressure, and heat stimuli, and TUG function tests before and after TENS application. Significance: This research will provide pilot data for future R01 funding to explore the longitudinal effect of TENS on chronic OA pain, functional ability and quality of life. It is the first to test a new placebo-TENS device and systematically examine the effect of TENS on a variety of physiological parameters (primary and secondary hyperalgesia) and clinical outcome measures (subjective pain at rest and with movement, function) in knee OA. These studies will further allow us to translate basic science experiments previously performed in animal models of arthritis to the clinical setting. By achieving a better understanding of the effect of TENS on pain associated with osteoarthritis, health care providers will be better able to use this non-drug strategy to improve pain control for older adults who are at risk for drug interactions and medication side effects. This will improve the functional status and independence of older adults suffering from this chronic, painful, limiting condition. [unreadable] [unreadable] [unreadable]